Scientists from David H. Koch Institute for Integrative Cancer Research at MIT and Harvard university report that they identified a previously unknown element in cancer cells’ metabolic pathways. They discovered that cancer cells can trigger alternative biochemical pathways that speeds up metabolism but diverts the by products for constructing new cells there by accelerating the multiplication.
“A normal cell doesn’t need to grow, but a cancer cell has to duplicate itself,” says Matthew Vander Heiden, assistant professor of biology and member of the David H. Koch Institute for Integrative Cancer Research at MIT.
Most human cells burn a six-carbon sugar called glucose. Through a long chain of reactions that require oxygen, the cells extract energy from the sugar and store it in molecular energy packets known as ATP. Cells use ATP to power a variety of functions, such as transporting molecules in and out of the cell, contracting muscle fibers and maintaining cell structure.
Glucose metabolism normally occurs in two stages, the first of which is known as glycolysis. It has been known for decades that cancer cells perform gylcolysis only, skipping the second stage, which is where most of the ATP is generated.
Scientists already knew that cancer cells replace one type of a key metabolic enzyme known as pyruvate kinase with another. Both versions of the enzyme (PKM1 and PKM2) catalyze the very last step of glycolysis, which is the transformation of a compound called PEP to the final product, pyruvate.
In the new study, the researchers found that PEP is involved in a previously unknown feedback loop that bypasses the final step of glycolysis. In cancer cells, PKM2 is not very active, causing PEP to accumulate. That excess PEP activates an enzyme called PGAM, which catalyzes an earlier step in glycolysis. When PGAM receives that extra boost, it produces even more PEP, creating a positive feedback loop in which the more PEP a cell has, the more it makes.
The most important result of this loop is that the cell generates a large pool of another chemical that is formed during an intermediate step of the reaction chain. Vander Heiden believes this compound, called 3-phosphoglycerate, is diverted into synthetic pathways such as the production of DNA, which can become part of a new cancer cell. In future studies, he plans to investigate how that diversion occurs.